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PubMed2003

The meaning of risk to first degree relatives of women with breast cancer.

Breast cancer represents a serious health concern for women. It is estimated that hereditary breast cancer accounts for approximately 5-10% of all breast cancer cases and as many as 25% of early-onset cases. We conducted a qualitative study of 26 first degree relatives of women with breast cancer (FDRs) in order to gain a deeper understanding of the effect of risk perception on their screening adherence. The method relied upon semi-structured, in-depth, face-to-face interviews with first degree relatives of women with breast cancer. We characterized FDRs by their response to a single query about their perceived risk. "Risk adopters" (N = 13) were defined as those who expressed a lifetime risk of breast cancer of 50% or more, and "normalizers" (N = 13) were those who indicated a lifetime risk of 49% or less. We conducted content analysis on the responses to the open-ended queries concerning perceived risk for breast cancer, searching for consistent themes among the responses. Surveillance behaviors were high among these FDRs relative to population-based comparisons. The difference between perceived and objective risk for breast cancer was significantly greater among risk adopters than normalizers (p < .0001). Three themes, derived from a content analysis of the FDR's natural language, further distinguish the two groups of women from one another: (1) causal attributions; (2) acceptance of labeling by the physician or other health care provider; and (3) current or remembered surveillance reminders from salient members of the social support network. We suggest different health care provider approaches to FDRs who are normalizers and those who are risk adopters, as well as additional studies of the impact of risk status (as manifest in the FDR's natural language) and surveillance behaviors, over time, among more diverse subgroups.

Adult↗

PubMed2002

Analysis of 5382insC (BRCA1) and 6174delT (BRCA2) mutations in 382 healthy Chilean women with a family history of breast cancer.

Breast cancer is the most common malignancy among women. Chilean studies reveal that this cancer presents the third highest mortality rate. A family history of breast cancer is one of the major risk factors for the development of this disease. BRCA1 and BRCA2 are the two main hereditary breast cancer susceptibility genes, and mutations in these genes are related to inherited breast cancer. In specific populations only some mutations have been found to be associated with susceptibility. The purpose of this study was to establish the frequency of 5382insC (BRCA1) and 6174delT (BRCA2) germline mutations in 382 healthy Chilean women with at least two relatives affected with breast cancer and in probands and their relatives from 8 high risk families for breast cancer, using mismatch PCR assay. The results obtained showed that 5382insC and 6174delT mutations were not found in either of the groups studied. The ethnic origin of the contemporary Chilean population and the data reported in the literature suggest that these mutations may be absent or have a very low frequency in this population.. This genetic study is part of a breast cancer screening program that also includes annual mammography and clinical breast examination over a five-year period. Strategies to reduce morbidity and mortality associated with breast cancer lie in early detection in women with genetic risk.

Adult↗

PubMed1999

Rehabilitation of breast cancer.

Breast cancer is a complicated disease treated with multimodality therapy. Adult women of any age can develop breast cancer, and most will be cured. Treatment of primary disease is associated with more side effects than the cancer. The process of metastatic cancer to death can be long. The entire family is affected by breast cancer whether early or late. A rehabilitation program must address the physical and psychosocial aspects of breast cancer, both at presentation and at recurrence. For a patient with early breast cancer, lifestyle changes may be important. A primary goal of a rehabilitation program is that each breast cancer patient should become well informed regarding treatment and its consequences (Table 9) in order to continue with her life. Treatment to recover the patient to her former physical and psychosocial state, and therapy for chronic problems from breast cancer or its treatment, requires an approach distinct from that given to other malignancies. Issues regarding survival prevail in any rehabilitation program for both early and late breast cancer.

Breast Neoplasms↗

PubMed1995

Palliative chemotherapy with CMF after the same adjuvant regimen for breast cancer. The Breast Cancer Study Group.

BACKGROUND: The results of palliative chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in patients with advanced breast cancer who received adjuvant therapy with the same regimen were investigated. RESULTS: Of 47 patients, 14 (30%) achieved an objective remission (median duration 9.5, range 5-21 months) and 8 (17%) stabilisation of disease (median duration 6, range 3-17 months). Objective remissions were observed in premenopausal as well as in postmenopausal women, in patients with all categories of dominant localisation of disease and regardless of the oestradiol receptor status of the primary tumour or eventual previous endocrine therapy. One of 4 and 13 of 43 patients who started palliative chemotherapy within or later than 12 months after the last adjuvant course obtained an objective remission. The median survival time from start of therapy of all treated patients was 12 (range 1-40) months. Patients with an objective remission or stable disease and patients with progressive disease had a median survival time of 20 (range 6-40) and 6 (range 1-35) months respectively (p < 0.0001). CONCLUSIONS: Palliative treatment with CMF should not be rejected for patients who have relapsed after adjuvant chemotherapy with the same modality.

Adult↗

PubMed2002

Role of steroid hormones and growth factors in breast cancer.

Breast cancer is the most common cancer in women worldwide and its incidence is increasing. Oestrogens and mitogenic growth factors may play an important role in the development of breast cancer, whereas inhibitory growth factors may prevent the development of breast cancer. Only about 5 to 10% of cases of breast cancer are due to inheritance of mutations in the BRCA1 or BRCA2 tumour suppressor genes. Mutations in the p53 tumour suppressor gene are commonly found in sporadic breast cancers. Retinoic acid and carotenoids may play a protective role in breast cancer since they inhibit the growth of the oestrogen receptor-positive MCF-7 breast cancer cell line. The presence of oestrogen and progesterone receptors predicts the likelihood of benefit from hormonal therapy. Amplification of the c-erbB2 oncogene in breast cancers is associated with a poor prognosis. It is now apparent that there is a complex, productive cross-talk between oestrogen-directed and growth factor-directed pathways which are believed to markedly reinforce their individual cellular effects on growth and gene responses.

Antineoplastic Agents, Hormonal↗

PubMed1997

A phase II trial of epirubicin plus paclitaxel in metastatic breast cancer. United Kingdom Coordinating Committee for Cancer Research Breast Cancer Sub-Committee.

Epirubicin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is an active combination for the treatment of metastatic breast cancer. A multicenter pilot phase II trial evaluated this combination in 35 patients treated with epirubicin 75 mg/m2 given as a 1-hour infusion, immediately followed by paclitaxel 200 mg/m2 given as a 3-hour infusion every 3 weeks. All patients had metastatic disease and had received a maximum of one chemotherapy regimen for advanced disease. A 43% response rate was observed in 30 evaluable patients, with two complete responses (7%) and 11 partial responses (37%). All patients were evaluable for toxicity. Hematologic toxicity was common and dose limiting. All patients underwent blood counts three times weekly. Grade 4 neutropenia was extremely common (91%), occurring at approximately days 10 to 12 and resolving rapidly in most cases. Thrombocytopenia was rare. Dose reductions were necessary in 10 patients, primarily for myelosuppression, but due to neuropathy in two patients. Alopecia was universal. Cardiac function was measured in all patients every two cycles. Among the first 24 evaluable patients, left ventricular ejection fraction decreased to below 40% in three patients, all of whom had received prior anthracyclines. Treatment was discontinued in one patient, who experienced no further deterioration. Under the auspices of the United Kingdom Coordinating Committee for Cancer Research, a randomized phase III study has been initiated in the United Kingdom to compare this combination of epirubicin/paclitaxel with combination epirubicin/cyclophosphamide. The primary end point of this study is progression-free survival, and the intention is to recruit 350 to 700 patients over the next 2 years.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Metallothionein as a prognostic biomarker in breast cancer.

Breast cancer is the most common cancer in women, with a general upward trend in incidence. Basic and clinical breast cancer research has continued at a rapid pace, in the endeavor to understand the biology of the disease so as to improve management of patients. Besides traditional pathological indicators, expression of molecular markers in breast cancer has also been comprehensively investigated. This paper will focus on the prognostic utility of metallothioneins (MTs), a family of low molecular weight metal binding proteins encoded by at least 10 functional MT genes that are associated with cell proliferation in breast cancer. Evidence that MT is a potential prognostic biomarker for breast cancer is supported by many reports in the literature. Expression of the MT protein has been detected by immunohistochemistry in a significant portion of invasive ductal breast cancers. MT expression has also been well studied in association with traditional clinico-pathological parameters of breast cancers. Generally, higher MT expression in breast cancers is predictive of worse patient outcomes. The relationship of MT isoforms to histological grade, estrogen receptor (ER) status, and prognosis will also be discussed.

Biomarkers, Tumor↗

PubMed1989

Sequential versus alternating regimens in the treatment of advanced breast cancer. Argentine Breast Cancer Cooperative Group.

With the object of proving whether sequential or alternate forms of chemotherapy would be advantageous one over the other in treating advanced breast cancer and with the purpose of evaluating two different anthracyclines at equimolecular doses in the above-mentioned alternating regimens, 250 patients who had received no prior chemo- or hormonotherapy were entered in a prospective randomized trial. Group A was administered 4-epiadriamycin and cyclophosphamide for 8 courses, followed by 6 cycles of CMF, and medroxyprogesterone acetate (MPA) from the beginning of therapy until progression. In group B, adriamycin + cyclophosphamide were alternated with CMF every two courses until 14 cycles were completed. Group C received 4'-epiadriamycin + cyclophosphamide alternated with CMF for 14 courses. In groups B and C, MPA was administered as in group A. Two hundred and twenty-four patients were evaluated. CR + PR were observed in 55.8% of group A, 43.4% of group B, and 46.4% of group C. Median duration of responses was 16 months (m) in group A, 13 m in group B and 20 m in group C, and median survival (CR + PR) was 16.5 m in group A, 16 m in group B and 24 m in group C. There were no statistically significant differences among the three groups in terms of response rate, duration of response and survival; furthermore, toxicity was moderate in all groups. At equimolecular doses there were no differences between adriamycin and epirubicin in the alternating schedules.

Adult↗

PubMed1984

Genetic predisposition to breast cancer.

Breast cancer risk factors are closely intertwined with the patient's cultural background, which may contribute to breast cancer aggregations within families. The difficult questions are: (1) does a truly hereditary breast cancer subset exist; (2) which familial aggregations are hereditary; and (3) is the hereditary form distinctive from its sporadic counterpart? These queries will be resolved once biomarkers are identified that show high sensitivity and specificity with genotype. The authors provide a review of this subject and will focus on their recent discovery of increased in vitro hyperdiploidy in cultured skin fibroblasts from patients with or at risk for hereditary breast cancer. The authors discuss findings from their study of family histories in 225 consecutively ascertained patients with verified breast cancer from the Creighton University School of Medicine Oncology Clinic. Findings consistent with an hereditary breast cancer syndrome were identified in 5% of the patients. Given the 112,000 new cases of breast cancer in the United States in 1982, the authors estimate that with a confidence coefficient of 0.95 between 2410 and 8790 of these individuals will manifest hereditary breast cancer. Specific surveillance/management programs should be geared to high-risk members of these families in which cancer yield will be predictable.

Adolescent↗

PubMed1998

Vorozole (Rivizor): an active and well tolerated new aromatase inhibitor for the treatment of advanced breast cancer patients with prior tamoxifen exposure. Investigational Drug Branch of the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer Cooperative Group.

Vorozole (Rivizor) is a potent and stereospecific inhibitor of aromatase having shown promising endocrine effects in phase I studies. In the present trial, 27 postmenopausal patients with advanced breast cancer, measurable lesions, presumably hormone responsive (ER or PR+, or ER? with disease-free survival longer than 1 year, or prior documented response to tamoxifen), were treated with vorozole one tablet 2.5 mg daily. All had been previously treated with tamoxifen as adjuvant (two patients) or for advanced disease (24 patients), or both (one patient). Objective remissions were observed in eight patients (30%) with two complete responses (CR) and six partial responses (PR) lasting for a median of 14.3 months (range 6.8-40.6); nine stabilizations were also recorded (median 7.9 months; range 3.7-40.1). Median time to progression for the 27 patients was 5.9 months. Sites of response were skin (three patients), lymph nodes (two patients), lung (two patients) and chest wall plus lymph nodes (one patient). Treatment was very well tolerated: mild hot flushes (four patients), gastrointestinal complaints (four patients) and no significant toxicity (common toxicity criteria grade above 2) or drug-related severe adverse event. It is concluded that vorozole is an active second-line endocrine treatment, deserving consideration for randomized comparison with other agents such as aminoglutethimide, megestrol acetate or medroxyprogesterone acetate.

Adult↗

PubMed2005

Radioimmunodetection and therapy of breast cancer.

Breast cancer is the second most-common cause of cancer death in women in the United States. Although more than 60% of patients can now be cured by initial treatment, the rest, although perhaps receiving palliation with currently available therapy, will die of their disease. Early detection of micrometastasis and improved treatment strategies are needed. Monoclonal antibody (mAb)-based imaging and tumor targeted therapy holds the potential to impact these problems. The most significant results of systemically administered antibody-based radiopharmaceuticals for detection and targeted therapy (radioimmunotherapy [RIT]) of breast cancer give strong evidence that this potential can be realized. Interest in immunoimaging recently has focused on small mAb modules used with 18F, 64Cu, or 124I to detect minimal disease in breast cancer by positron emission tomography or single-photon emission computed tomography. Reported therapy trials in advanced breast cancer have yielded objective responses and minimal toxicity. These studies have spanned several radionuclides as well as several mAb, fragments and approaches, including dose intensification with bone marrow support; combined therapy with other modalities (ie, CM-RIT); biodegradable peptide linkers; and pretargeting. RIT evaluated in clinical breast cancer trials has delivered as much as 4000 cGy to metastatic breast cancer per therapy dose with marrow stem cell support. Preclinical studies have demonstrated further promising strategies for breast cancer. RIT studies must address the key issue: enhancing the therapeutic index (tumor effect verses most sensitive normal tissue (bone marrow) effect). Approaches now include newly engineered mAb, scFv modular constructs, blood clearance on demand, enhanced pretargeting, applications of both alpha and beta emitting radionuclides, and combination therapy using molecular triggers for therapeutic synergy. These strategies for detection and treatment of metastatic breast cancer should lead to notable clinical impact on management and cure of breast cancer.

Antibodies, Monoclonal↗

PubMed2000

BRCA1 mutations and clinicopathological features in a sample of Italian women with early-onset breast cancer.

Breast cancer in young women is uncommon and often presents with unfavourable biopathological features. Although early age at onset could suggest a genetic susceptibility to cancer, the appropriateness of BRCA1 testing for women with early-onset breast cancer and modest family history (FH) is controversial. 40 Women diagnosed with breast cancer at the age of 35 years or less, unselected for FH, were screened for germ line BRCA1 mutations by automated sequencing of exons 2, 5, 6, 11, 13 and 20. Overall, deleterious mutations were evidenced in 6 (15%) patients. With regard to FH, mutations were detected in 14%, 11% and 29% of women with none, weak and strong FH, respectively. Large tumour size, grade 3, lack of oestrogen receptors and high proliferation rate were significantly more common in mutation carriers (MC). Our data support both the appropriateness of testing young breast cancer patients and the frequency of unfavourable features in BRCA1-related breast cancer. It is hypothesised that BRCA1 mutations partially justify the high rate of aggressive breast cancer in young patients and that combining age and breast cancer phenotype could help to identify probable MC.

Adult↗

PubMed1995

A quality-adjusted survival meta-analysis of adjuvant chemotherapy for premenopausal breast cancer. International Breast Cancer Study Group.

The purpose of this paper is to develop and apply a meta-analysis methodology, that does not require patient-level data, for comparing treatments in terms of quality-of-life-adjusted survival. As a motivating example, we considered adjuvant chemotherapy for breast cancer. This therapy has been shown to offer an improvement in recurrence-free and overall survival, especially for younger women, but its acute toxic effects discourage some physicians from prescribing it. To determine whether the benefit of adjuvant chemotherapy treatment outweighs its costs in terms of toxic effects, we performed a meta-analysis of quality-adjusted survival based on data from 1229 patients, 49 years of age or younger, randomized in eight clinical trials that compared chemotherapy versus no adjuvant systemic therapy. We conducted the meta-analysis by performing a quality-adjusted survival analysis known as a Q-TWiST analysis on each trial. A Q-TWiST analysis allows one to make treatment comparisons that incorporate differences in quality of life associated with various health states. In this analysis, we define as health states the periods of time patients spend: (i) with subjective toxic effects of chemotherapy; (ii) without symptoms of recurrence and toxicity, and (iii) following disease recurrence. We assigned weights to each health state which reflect their relative value in terms of quality of life and allowed them to vary in a sensitivity analysis. We then combined the individual trial results in a meta-analysis, using a multivariate regression model, in such a way that we could easily perform an overall sensitivity analysis. Individual patient-level data are not required to perform this meta-analysis methodology if the individual Q-TWiST analysis results for each trial are available.

Adult↗

PubMed2005

Examining the influence of coping with pain on depression, anxiety, and fatigue among women with breast cancer.

Breast cancer treatment can have a profound influence on a woman's physical, psychological, social, and spiritual well-being. Anxiety, depression, anger, fatigue, and fear of recurrence are common responses to a diagnosis of breast cancer and undergoing breast cancer treatment. Women develop their own coping strategies for the pain and other effects of treatment. However, it is unclear whether there is a relationship between adaptation to pain and psychological distress during breast cancer treatment. Findings from the present study reveal that breast cancer patients who have better pain coping strategies also have lower levels of anxiety, fatigue and depression. These results suggest that pain coping interventions may reduce fatigue and psychological distress among women with breast cancer.

Adaptation, Psychological↗

PubMed2002

Estrogen receptor downregulators: new advances in managing advanced breast cancer.

Breast cancer is the most frequently diagnosed malignancy in American women. Although potentially curable in the early stage, metastatic breast cancer, however, is essentially incurable. Because metastatic breast cancer is unlikely to be cured with currently available therapies, the goals of treatment in this setting are prolonging survival and maintaining or improving the quality of life. In patients with receptor (estrogen or progesterone)-positive metastatic breast cancer, endocrine therapy is generally considered the preferred first-line therapy because of the superior tolerability and the similar efficacy when compared with chemotherapy. Today a variety of endocrine therapies are available for the treatment of metastatic breast cancer, among which tamoxifen is the most widely used. Despite its proven efficacy and safety, a significant proportion of patients do not respond to tamoxifen. Further, due to its partial estrogenic activity, tamoxifen is associated with an increased risk of thromboembolism and endometrial cancer. Agents without any estrogenic activity-estrogen receptor downregulators have therefore been developed. Fulvestrant is the first clinically proven agent of this class. Oncology nurses have a key role in managing and educating patients with breast cancer. This supplement provides nurses with an overview of existing and emerging endocrine therapies for postmenopausal patients with metastatic or advanced breast cancer.

Antineoplastic Agents, Hormonal↗

PubMed1993

Role of nutrition in women's health: diet and breast cancer.

Breast cancer, which is the most frequently diagnosed malignancy in women today, remains a major threat. As the incidence increases at 1% to 2% annually, breast cancer strikes about 182,000 US women each year and kills 46,000. Known risk factors, such as age, early menarche, late age of first pregnancy, late menopause, family history, and obesity, account for only 40% to 50% of breast cancer cases. Consequently, the etiology of 50% to 60% of cases is unknown. Perhaps no area is more controversial than the link between nutrition and cancer, in particular the association between dietary fat and the development of breast cancer. Findings from animal research and international correlation studies indicate a causal relationship between fat intake and breast cancer. A recent analysis of 12 case-control studies among postmenopausal women also showed a 50% increase in relative risk among women ingesting high intakes of saturated fat. Furthermore, analyses of postmenopausal women in Hawaii estimated that 10% to 20% of breast cancer could be prevented by notably decreasing saturated fat intake. Nevertheless, epidemiologic studies (case-control and cohort) give conflicting results regarding the causal relationship between fat intake and breast cancer. The fact that these studies have failed to consistently show a significant association between dietary fat and breast cancer risk may be attributable to the difficulty of collecting accurate dietary information and other methodologic limitations. Findings are also limited by the lack of data on the influence of a high-fat diet during childhood.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1991

Adjuvant therapy of breast cancer. International Breast Cancer Study Group.

Adjuvant systemic therapy has been shown to reduce relapses in treated women and to prolong their survival. This is true for all studied subpopulations. Multidrug chemotherapy for the duration of 6 months for the premenopausal patients, and tamoxifen or short-term chemotherapy with long-term tamoxifen for the postmenopausal patients represent the treatments of choice to reduce the risk of relapse. Some of the high priority questions relate to i) the definition of a population for which the risk of relapse is low enough to avoid the use of systemic adjuvant therapy, and ii) the definition of an optimal way of using available adjuvant therapies. These might find answers from ongoing research. The modest but real improvement of the prognosis in operable breast cancer was exclusively obtained only by means of clinical trials, and it is mandatory that participation in programs of clinical research becomes medically and socially the treatment of choice.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

International nursing and breast cancer.

Breast cancer is the most common cancer in women worldwide and its incidence is increasing in most countries. Nurses involved in breast cancer care have an impact on early detection of breast cancer, treatment, and symptom management, and they serve as advocates for women with the disease. In many countries nurses are far more numerous than physicians, and nurses are in an ideal position to influence breast cancer care. The International Society of Nurses in Cancer Care (ISNCC) is an organization representing more than 50,000 oncology nurses in 25 countries. The society provides a communication network for national and regional cancer nursing societies and communication on developments in cancer nursing to nurses working in countries where a national cancer nursing group does not exist. The society also acts as a resource for nurses in practice, education, research, and management, and it serves as a link for other international, regional, national, and local organizations in promoting collaboration to achieve ISNCC's goals. In collaboration with the Susan G. Komen Breast Cancer Foundation, the society developed a 2-day "train-the-trainer" workshop for a selected group of cancer nurses from around the world. The workshop includes didactic presentations, skills instruction, and demonstrations that cover the continuum of breast cancer care. Participants have represented the countries of Brazil, Colombia, China, Italy, Spain, Portugal, Turkey, Pakistan, Australia, Germany, South Africa, Greece, and India. They have subsequently developed educational programs for nurses and the public in their countries, started support groups, published educational materials on breast cancer, and participated in political activities. These advances indicate that despite challenges such as nursing shortages and a lack of resources, cancer nurses are making a difference internationally.

Awareness↗